The successful treatment of cancer has allowed a large proportion of patients to survive for long periods of time. Long-term survivors, however, face new problems, among which the development of second malignancies and adverse reproductive effects are the most serious. This study of genetic susceptibility to the development of adverse outcomes in Hodgkin's disease patients, treated with different therapies, will incorporate newly collected epidemiologic information with already existing cytogenetic and treatment data. A longitudinal study of 225 adult Hodgkin's disease patients diagnosed at the University of Texas M.D. Anderson Cancer Center from 1987 to 1992 is planned. These patients have been enrolled in a study of genotoxic effects of chemotherapy since their diagnosis. Blood samples have been collected at time of diagnosis, during treatment, and multiple points after therapy. We propose to collect epidemiologic and vital status information on these patients through personal or phone interviews. These data will be integrated with the available cytogenetic and therapeutic data to analyze individual susceptibility to treatment genotoxicity at baseline (pretreatment), during, and after treatment. We will also evaluate whether the short-term markers (sister chromatic exchange and chromosome break frequencies) used to assess mutagen sensitivity can be used as genetic markers to identify patients at high risk of developing a second malignancy. The identification of such biomarkers would be of great importance in the prevention of secondary cancer. This approach could be extended to other arger cohorts of cancer patients at risk of developing therapy-related cancers.